Puerto Rican adults living on the mainland US have documented health disparities; however, little research has been conducted with this second largest Hispanic subgroup. Our long-term goal is to understand the complex interactions of diet and other behavioral and environmental factors, genetics, and psychosocial stress on the high and apparently increasing prevalence of cardiovascular disease (CVD) risk factors in Puerto Rican adults. As this group is rapidly growing, understanding the reasons for this risk is of great importance. Our initial funding period for the Boston Puerto Rican Center on Population Health and Health Disparities (BPR-CPHHD, 2003-08) focused on the role of stress on physical disability and cognitive decline, through physiological dysregulation or allostatic load. During that investigation, it became clear that risk factors for CVD were highly prevalent. These findings are in contrast to the commonly held belief that there is a Hispanic paradoxlower heart disease and mortality despite greater poverty. Importantly, the Puerto Rican population differs considerably in ancestral genetic history and in exposures to known risk factors from other Hispanic groups. They have unique dietary intake patterns, as well as social, cultural and environmental structures that contribute and affect reaction to stressors. During our initial funding period, we successfully assembled a cohort of 1450 Puerto Rican adults, aged 45-75 years at baseline, and have completed (to date) more than 900 two-year follow-up interviewswe are continuing, with the expectation of completing at least 1150. As this population is aging and growing rapidly, the high prevalence and apparent cohort effect of increased heart disease risk factors suggest that 1) this population has serious health disparities in heart disease risk factors and 2) heart disease will become an even greater problem for this group in the near future. Our overall aim for this renewal is, therefore, to extend follow-up and to measure and analyze relevant characteristics and CVD risk factors, and to add additional contextual and outcome measures for CVD risk in this established cohort of Puerto Rican adults, so that we may better understand the dynamics of these disparities. Our model follows the transdisciplinary cells to society concept developed jointly with our partner CPHHDs during the initial funding period, with consideration of genetic variation in relation to longitudinal change in allostatic load and biochemical indicators of risk, to more concrete indicators of disease (ankle brachial index (ABI) and intima media thickness (IMT)); with additional focus on social networks, neighborhood characteristics (physical space and access to food) and environment (air pollution) factors as social determinants of health. Finally, using community based participatory techniques, we will implement and test a multidimensional intervention that focuses on diet and exercise, but that also fully considers the social and physical environment to ensure success. With participation of our community partner. La Alianza Hispana, and the support of our administrative, biostatistics and laboratory cores, our team is efficiently poised to make significant contributions to understanding the factors that contribute to the apparent growing threat of heart disease in this highly disadvantaged groupwhile providing insights that may be useful to other vulnerable groups. The continuation of our cohort, with its rich constellation of measures, will allow us to unravel some of the complex etiologic interactions which contribute to CVD risk, so that effective interventions maybe implemented.